Antiosteoporotic Effects Of Bisphosphonate And Nitric Oxide Donor On Ovariectomized Rats

Osteoporosis is a chronic,progressive disease of the skeleton characterized by bone fragility due to a reduction in bone mass and possibly alteration in bone architecture which leads to a propensity to fracture with minimum trauma. Osteoporosis is a systemic disease.The mortality and morbidity of this disease is high over the world nowadays.It is closely related to dental diseases and treatments,such as periodontits,dentures rehabilitation,othodontics treatment and implantation.Development with the aging progression,more and more the elderly patients want to rehabilitate missing teeth by implants.So we now pay attention to the methods how to improve implans successfully.Liu hong-chen,et al.had finished many cellular studies in this field.The aim of our study was to evaluate the effects of antiosteoporotic drugs,to compare and find the effective dose of new drug,to explore the bone remodeling features of the OVX rats and to find changes of the mandibles in the OVX rats.It was expected to provide experimental evidence for improving osseointegration with new medicine administration system of dental implant.This study was consisted of four tests:TestⅠ:Establishment and evaluation the osteoporosis model of ovariectomized ratsObjective:To establish and evaluate the osteoporosis model of ovariectomized rats.Methods:Nity-six female Sprague-Dawley(SD)rats aged 12 weeks were divided into sham group twenty-four rats and OVX group seventy-two rats.Rats in OVX group were ovariectomized and rats in sham group were removed some fat tissue.After three months,Sixteen rats from OVX group and sham group respectively were anesthetized.Blood samples were withdrawn to assess biochemical markers of bone metabolism.At sacrifice,the femora and tibia were separated,cleaned of soft tissues.MicroCT scanning,bone histomorphometric analysis and histopathological observation,biomechanical testing were progressed gradually.The data were statistically analyzed by SPSS13.0.Results:The operations were made successfully.After three months,there is significant difference of body weights between OVX rats and sham rats.Serum ALP activity and osteocalcin levels elevated significantly in OVX group than Sham group(P＜0.05).Trabecular bone volume and area,trabecular thickness, trabecular number,BMC and BMD of OVX group all were reduced than those of Sham group(P＜0.05).Trabecular separation increased significantly.Compared with sham group,elastical load of OVX group increased(P＜0.05).Maximal stress and elastical stress deceased significantly.Conclusion:Ovariectomy is facility to operate.After three months,the OVX rats are in osteoporotic status.Body weight increases significantly.Bone mass is reduced.Trabecular bonearchitecture has changed.And bone biomechanical performance is worsening..TestⅡ:Compared study between mandible and tibia of the OVX ratsObjective:To compare the performance in mandible with that in tibia of the OVX rats after ovariectomized three months.Methods:Sixteen rats from OVX group and sham group were anesthetized, then sacrificed.After microCT scanning,histopathological observation were made.The data were statistically analyzed by SPSS13.0.Results:After rats ovariectomized three months,trabecular bone volume, trabecular thickness,trabecular number,BMC and BMD of OVX group all were elevated than those of Sham group(P＜0.05).Trabecular separation was reduced statistical significantly.The changes of mandible after ovariectomized three months were opposite when compared with those of tibia.Compared with sham group,marrow cavity of trabecular bone under molars in OVX group expanded, trabecular bone area and new bone matrix in alveolar bone decreased. Conclusions:There are different appearances in trabecular bone morphology and architecture between tibia and mandible.After three months,changes in tibia and mandible are different dramatically.The tibia of OVX rat is in osteoporotic status.But bone mass of the OVX mandible increased.Trabecular bone architecture is more dense.Deeply studies are needed.TestⅢ:Experimental study of L-Arg effects on OVX ratsObjective:To evaluate different dose antiosteoporotic effects of L-Arg on OVX rats.Methods:Thirty-two rats from OVX group and eight rats from sham group were subdivided into five groups.A 4-week daily treatment(5 days a week, Monday-Friday)consisting of s.c.injections of 5mg/kg,10mg/kg,20mg/kg L-Arg were respectively given to the OVX drug groups.Sham and OVX groups were given physiological saline as control.At the end of the treatment period the rats were anesthetized.Blood samples were withdrawn to assess biochemical parameters.At sacrifice,the femora and tibia were separated,cleaned of soft tissues.MicroCT scanning,bone histomorphometric analysis and histopathological observation,biomechanical testing were progressed gradually. The data were statistically analyzed by SPSS13.0.using One-Way ANOVA method.Results:Data from L-Arg 10mg/kg group were identical or better than those from sham group.Data from L-Arg5mg/kg group were a little worse than those from L-Arg10mg/kg group.Maximal stress of L-Arg5mg/kg was different from that of sham group significantly.(P＜0.05)Trabecular bone connected into mashwork.But many fractures were seen in trabecular bone.Most data from L-Arg20mg/kg group were worse than those from OVX group.Only maximal stress and elastical stress were higher significantly than those from OVX group. No significant difference between L-Arg20mg/kg group and sham group.Conclusions:The effects of three different dose L-Arg on OVX rats are discrepant significantly.Out of them,L-Arg10mg/kg group has the best antiosteoporotic effect.TestⅣ:Experimental study of effects on OVX rats treated with alendronate and L-arginineObjective:To evaluate the effects of alendronate and L-arginine on the OVX rats.To explore the mechanism of these drugs tentatively.Methods:Thirty-two rats from OVX group and eight rats from sham group were subdivided into five groups.A 4-week treatment consisting of s.c.injections of Alendronate 1.5mg/kg(twice a week,on Monday and Thursday)and/or L-Arg 10mg/kg daily(5 days a week,Monday-Friday),were respectively given to the OVX drug groups.Sham and OVX groups were given PHYSIOLOGICAL SALINE as control.At the end of the treatment period the rats were anesthetized. Blood samples were withdrawn to assess biochemical parameters.At sacrifice,the femora and tibia were separated,cleaned of soft tissues.MicroCT scanning, bone histomorphometric analysis and histopathological observation, biomechanical testing were progressed gradually.The data were statistically analyzed by SPSS13.0.using One-Way ANOVA method.Results:Data from ALN or L-Arg10mg/kg group were identical.Maximal stress and elastical stress of ALN group were significant higher than those of OVX group.No significant difference between ALN group and sham group. Although maximal stress and elastical stress of L-Arg10mg/kg group and the combination treatment of ALN and L-Arg group were increased compared to OVX group,no significant difference between them.Conclusions:The effects of three different drug on OVX rats are discrepant significantly.ALN or L-Arg group has the better antiosteoporotic effect than the combination treatment of ALN and L-Arg group.The combination maybe oversuppresses bone resorption and decrease bone formation.